Sleep difficulties are a major motivation for use of drugs. The most often selected drugs are those interacting with the GABA neurotransmitter-receptor system in the brain, the so-called minor tranquillisers, of which the group of benzodiazepine drugs is the classic example. Disadvantages of currently available hypnotics are the potential for adverse reactions, remaining lesser quality of sleep, hangover effects, dependency potential, withdrawal effects and undesirable effects on cognitive functioning. The quality of sleep can not only be derived from the effect of sleep, for example whether the sleep has been refreshing and has a positive effect on daytime drowsiness/alertness the morning after, but also from objective EEG determined characteristics, describing sleep stages and architecture.
The discovery of different types of benzodiazepine receptors are exploited to open new avenues for pharmaco-therapy of insomnia (for review see C. K. Kirkwood; Management of insomnia; J Am Pharmaceut. Ass. Vol 39 pp 688-696; 1999). Other mechanisms for inducing sleep are also explored. The opiate-like drugs, the barbiturates and anti-histamines are drug classes which have been used several decades ago as sleep inducers, but their use became obliterated due to undesirable side effects and/or lesser efficacy. Such drugs are still in use for other disorders whereby the main effects would be side effects when used for the treatment of sleep disorders. Specifically, drugs, antagonising histamine receptors are sedative and sleep inducing but are not used regularly anymore for the treatment of sleep disorders in view of lower selectivity, lower potency and lower safety in comparison to benzodiazepines and their modern successors.
Mirtazapine is known as an anti-depressant. It is active for that purpose at daily doses of 15-45 mg per person. It is well-known that the dose is crucial for effective therapy, in particular for the treatment of depression. Mirtazapine is reported to have some initial sedative effects and because of this its effects on sleep have been investigated. It is reported that in the dose range of 5-30 mg per person per day improvement of transient, or situational insomnia is found, whereby the dose of 15 mg was reported to be preferable over 5 mg (Sørensen et al. Acta Psychiatr. Scand. 71: 339-346; 1985). Also Winokur (Biological Psychiatry 1998; 45(8S): p 106S) investigates 15 and 30 mg mirtazapine in depressed patients with prominent sleep related complaints and recommends further investigation of these doses for treatment of sleep disorders.